A Study of Two Dosing Schedules of Atezolizumab in Combination With Gemcitabine and Cisplatin as First-Line Treatment for Metastatic Bladder Cancer

NCT03093922 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 16-1621
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to compare any good and bad effects the study drug atezolizumab has on the cancer when combined with the standard chemotherapy drugs gemcitabine and cisplatin (or GC) in two different dosing schedules: chemotherapy (GC) before atezolizumab vs. GC after atezolizumab.

Conditions

Urothelial Carcinoma; Locally Advanced; Unresectable

Keywords

Gemcitabine; Atezolizumab; Cisplatin; 16-1621

Outcome Measures

Primary Outcomes (1)

• overall response rate

  with response determined according to RECIST v1.1

  1 year

Study Arms (3)

Atezolizumab alone with Gemcitabine and Cisplatin

EXPERIMENTAL

Atezolizumab alone for 2 cycles. One treatment cycle equals 21 days. Then patient will receive combined atezolizumab and Gemcitabine and Cisplatin for 6 cycles. All 8 treatment cycles will take approximately 24 weeks. If carboplatin is substituted for cisplatin, eGFR for dosing may be calculated by institutional standard formulas, at the discretion of the treating investigator. This cohort is NO LONGER ACCRUING patients since 5/22/2018.

Drug: Atezolizumab; Drug: Gemcitabine; Drug: Cisplatin

Atezolizumab with Gemcitabine and Cisplatin

EXPERIMENTAL

Gemcitabine and Cisplatin for 2 cycles. One treatment cycle equals 21 days. After 2 cycles of Gemcitabine and Cisplatin patient will receive combined atezolizumab and Gemcitabine and Cisplatin for 4 cycles. All 6 treatment cycles will take approximately 18 weeks. If carboplatin is substituted for cisplatin, eGFR for dosing may be calculated by institutional standard formulas, at the discretion of the treating investigator.

Drug: Atezolizumab; Drug: Gemcitabine; Drug: Cisplatin

Atezolizumab alone for 1 cycle prior to gemcitabine, cisplatin

EXPERIMENTAL

Atezolizumab alone for 1 cycle. One treatment cycle equals 21 days. After 1 cycle of atezolizumab the patients will receive combined atezolizumab and gemcitabine, cisplatin for 4 cycles. All 5 treatment cycles will take approximately 15 weeks. Cisplatin dose can be given on day 1 or split over days 1 and 8 at the investigator"s discretion. Once the split-dose cisplatin is used, it should be used for the remainder of the chemotherapy treatment course.

Drug: Atezolizumab; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Atezolizumab DRUG

1200 mg/m\^2

Atezolizumab alone for 1 cycle prior to gemcitabine, cisplatin; Atezolizumab alone with Gemcitabine and Cisplatin; Atezolizumab with Gemcitabine and Cisplatin

Gemcitabine DRUG

1000 mg/m\^2

Atezolizumab alone for 1 cycle prior to gemcitabine, cisplatin; Atezolizumab alone with Gemcitabine and Cisplatin; Atezolizumab with Gemcitabine and Cisplatin

Cisplatin DRUG

70 mg/m\^2

Atezolizumab alone for 1 cycle prior to gemcitabine, cisplatin; Atezolizumab alone with Gemcitabine and Cisplatin; Atezolizumab with Gemcitabine and Cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed urothelial carcinoma of the bladder, ureter, urethra, or renal pelvis by the enrolling institution. Patients with mixed histologies are required to have a predominant urothelial component as reviewed by the pathologist at the enrolling institution.
• Locally advanced (T4b, any N: any T, N2-3) or metastatic (M1) disease as determined by the treating investigator.
• Age ≥18 years
• Life expectancy ≥ 12 weeks
• The patient must have measurable disease according to RECIST v1.1 and must have one site amenable to biopsy that, in the opinion of the investigator and/or interventional radiologist, is likely to yield acceptable tumor sample for a core biopsy per the below pathology criteria.
• Subject must agree to undergo two research-directed biopsies during treatment.
• Patients must have adequate tumor tissue available for PD-L1 testing. Adequate tumor tissue is defined as:
• For core-needle biopsy specimens, at least three cores should be submitted for evaluation if feasible. Acceptable samples include core-needle biopsies for deep tumor tissue (minimum of three cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. Samples collected from fine-needle aspiration, brushing, cell pellet from pleural effusion, bone metastases without a soft tissue component, and lavage are not acceptable.
• For pre-treatment archival tissue, representative urothelial carcinoma FFPE tumor specimens (tumor blocks or 30 unstained slides) must be provided. Patients with \< 30 slides may be enrolled after discussion with the MSK Principal Investigator.
• Primary or metastatic specimens (with the exception of bone because it is not evaluable for PD-L1 expression) may be submitted.
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1):
• ANC ≥ 1500 cells/uL
• WBC counts \> 2500/uL
• Lymphocyte count ≥ 300/uL
• Platelet count ≥ 100,000/uL; Hemoglobin ≥ 9.0 g/dL

You may not qualify if:

• Prior chemotherapy or immunotherapy for metastatic urothelial cancer. Prior neoadjuvant or adjuvant chemotherapy with first progression \> 12 months is allowed. Prior intravesical treatments such as BCG are allowed, however no BCG is allowed within 4 weeks prior to initiation of study treatment.
• Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed:
• Hormone-replacement therapy or oral contraceptives
• Herbal therapy \> 1 week prior to Cycle 1, Day 1. Herbal therapy intended as anticancer therapy must also be discontinued at least 1 week prior to Cycle 1, Day 1.
• Palliative radiotherapy for bone metastases \> 2 weeks prior to Cycle 1, Day 1
• Bisphosphonate therapy for symptomatic hypercalcemia
• °Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed.
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
• Patients with a history of or active bone marrow disorders expected to interfere with study therapy (e.g. acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma)
• Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
• Evaluable or measurable disease outside the CNS
• No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
• No history of intracranial hemorrhage or spinal cord hemorrhage
• No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted.
• No neurosurgical resection or brain biopsy within 28 days prior to Cycle 1, Day 1

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Ohio State University: collaborator
• University of Chicago: collaborator
• Genentech, Inc.: collaborator
• Targos: collaborator

Study Sites (9)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

atezolizumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Samuel Funt, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized phase II study testing two different schedules of atezolizumab combined with gemcitabine and cisplatin chemotherapy (GC) in patients with metastatic urothelial carcinoma (mUC) who are eligible for cisplatin.

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: March 28, 2017
• Study Start: March 22, 2017
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: April 22, 2025

Record last verified: 2025-04

Locations

US (9)